Bob Arctor
Robert ("Bob") Arctor is an undercover narcotics agent posing as a drug addict in a house he shares with a few other men. Throughout the novel, he wears a shape-obscuring suit that allows him to have anonymity when dealing with his government employers. As the story progresses, it becomes clear that being addicted to Substance D has impacted Arctor's brain, causing him to split almost entirely into two different personalities. The novel's plot is essentially concerned with the unraveling of Arctor's mind.
Donna Hawthorne
Donna is a dealer, a sly operator who deals Substance D to the addicts for a profit. Charismatic yet emotionally untouchable, she is more or less Arctor's girlfriend, although his true feelings are unrequited. It is later revealed that she is also an undercover narcotics operative for the government, a development Arctor himself didn't realize.
Jim Barris
Barris is one of Arctor's housemates. He is a strange, inscrutable man with confusing habits and an almost inhuman psychology. He is revealed to be the most demented of the crew, and, through surveillance footage from the cameras Arctor installed on his own house, the detectives realize that he's been trying to synthesize a new type of drug through repeated experimentation.
Charles Freck
Another one of Arctor's addict friends, Freck is a casually interesting man with more humanity than most of the other characters put together. He eventually goes crazy and tries to kill himself, but his attempt fails (having taken hallucinogens instead of poison) and simply sinks him deeper into his misery.
Jerry Fabin
Fabin is another one of Arctor's acquaintances who is addicted to drugs. He actually serves as the book's hook, being the man who hallucinated the many bugs living in his hair and tormenting him, despite the fact that no one else can see them. Jerry is one of the novel's most comical characters, but in light of the depressing nature of Substance D and drug abuse, his comical nature suddenly seems terribly macabre.
